Correcting for Targeted and Control Agent Signal Differences in Paired-Agent Molecular Imaging of Cancer Cell-Surface Receptors

Paired-agent kinetic modeling protocols provide one means of estimating cancer cell-surface receptors with in vivo molecular imaging. The protocols employ the coadministration of a control imaging agent with one or more targeted imaging agent to account for the nonspecific uptake and retention of the targeted agent. These methods require the targeted and control agent data be converted to equivalent units of concentration, typically requiring specialized equipment and calibration, and/or complex algorithms that raise the barrier to adoption. This work evaluates a kinetic model capable of correcting for targeted and control agent signal differences. This approach was compared with an existing simplified paired-agent model (SPAM), and modified SPAM that accounts for signal differences by early time point normalization of targeted and control signals (SPAMPN). The scaling factor model (SPAMSF) outperformed both SPAM and SPAMPN in terms of accuracy and precision when the scale differences between targeted and imaging agent signals (α) were not equal to 1, and it matched the performance of SPAM for α  =  1. This model could have wide-reaching implications for quantitative cancer receptor imaging using any imaging modalities, or combinations of imaging modalities, capable of concurrent detection of at least two distinct imaging agents (e.g., SPECT, optical, and PET/MR)

Quantifying Cancer Cell Receptors with Paired-Agent Fluorescent Imaging: a Novel Method to Account for Tissue Optical Property Effects.

Dynamic fluorescence imaging approaches can be used to estimate the concentration of cell surface receptorsin vivo. Kinetic models are used to generate the final estimation by taking the targeted imaging agent concentration as a function of time. However, tissue absorption and scattering properties cause the final readout signal to be on a different scale than the real fluorescent agent concentration. In paired-agent imaging approaches, simultaneous injection of a suitable control imaging agent with a targeted one can account for non-specific uptake and retention of the targeted agent. Additionally, the signal from the control agent can be a normalizing factor to correct for tissue optical property differences. In this study, the kinetic model used for paired-agent imaging analysis (i.e., simplified reference tissue model) is modified and tested in simulation and experimental data in a way that accounts for the scaling correction within the kinetic model fit to the data to ultimately extract an estimate of the targeted biomarker concentration

Use of PCR to identify Leptospira in kidneys of big brown bats (Eptesicus fuscus) in Kansas and Nebraska, USA

Bats have been implicated as potential carriers of Leptospira as a result of surveys, mostly in Australia and South America. We measured the prevalence of pathogenic leptospires in kidneys of bats from Kansas and Nebraska. From 7 August 2012 to 21 August 2012, we extracted DNA from kidneys of 98 big brown bats (Eptesicus fuscus) submitted and found negative for rabies. The DNA was processed in a two-step, seminested PCR assay with a dual-labeled Taqman probe specific for pathogenic leptospires. As a negative control, we used a saprophytic leptospire (Leptospira biflexa Patoc) and, as a pathogenic control, Leptospira interrogans Canicola. All bat kidneys were negative for pathogenic leptospires, suggesting that it is unlikely that the big brown bat, one of the most prevalent bat species in North America, is a reservoir for transmission of leptospires to dogs or humans

Radio astronomy

The following subject areas are covered: (1) scientific opportunities (millimeter and sub-millimeter wavelength astronomy; meter to hectometer astronomy; the Sun, stars, pulsars, interstellar masers, and extrasolar planets; the planets, asteroids, and comets; radio galaxies, quasars, and cosmology; and challenges for radio astronomy in the 1990's); (2) recommendations for new facilities (the millimeter arrays, medium scale instruments, and small-scale projects); (3) continuing activities and maintenance, upgrading of telescopes and instrumentation; (4) long range programs and technology development; and (5) social, political, and organizational considerations

Getting out and about in older adults: the nature of daily trips and their association with objectively assessed physical activity

<p>Abstract</p> <p>Background</p> <p>A key public health objective is increasing health-enhancing physical activity (PA) for older adults (OAs). Daily trip frequency is independently associated with objectively assessed PA volumes (OAs). Little is known about correlates and these trips' transport mode, and how these elements relate to PA. Purpose: to describe the frequency, purpose, and travel mode of daily trips in OAs, and their association with participant characteristics and objectively-assessed PA.</p> <p>Methods</p> <p>Participants (n = 214, aged 78.1 SD 5.7 years), completed a seven-day trips log recording daily-trip frequency, purpose and transport mode. Concurrently participants wore an accelerometer which provided mean daily steps (steps·d^-1), and minutes of moderate to vigorous PA (MVPA·d^-1). Participants' physical function (PF) was estimated and demographic, height and weight data obtained.</p> <p>Results</p> <p>Trip frequency was associated with gender, age, physical function, walking-aid use, educational attainment, number of amenities within walking distance and cars in the household. Participants reported 9.6 (SD 4.2) trips per week (trips·wk^-1). Most trips (61%) were by car (driver 44%, passenger 17%), 30% walking or cycling (active) and 9% public transport/other. Driving trips·wk^-1were more common in participants who were males (5.3 SD 3.6), well-educated (5.0 SD 4.3), high functioning (5.1 SD 4.6), younger (5.6 SD 4.9), affluent area residents (5.1 SD 4.2) and accessing > one car (7.2 SD 4.7). Active trips·wk^-1were more frequent in participants who were males (3.4 SD 3.6), normal weight (3.2 SD 3.4), not requiring walking aids (3.5 SD 3.3), well-educated (3.7 SD 0.7), from less deprived neighbourhoods (3.9 SD 3.9) and with ≥ 8 amenities nearby (4.4 SD 3.8).</p> <p>Public transport, and active trip frequency, were significantly associated with steps·d^-1(p < 0.001), even after adjustment for other trip modes and potential confounders. Public transport, active, or car driving trips were independently associated with minutes MVPA·d^-1(p < 0.01).</p> <p>Conclusions</p> <p>Daily trips are associated with objectively-measured PA as indicated by daily MVPA and steps. Public transport and active trips are associated with greater PA than those by car, especially as a car passenger. Strategies encouraging increased trips, particularly active or public transport trips, in OAs can potentially increase their PA and benefit public health.</p

Three-dimensional organotypic co-culture model of intestinal epithelial cells and macrophages to study Salmonella enterica colonization patterns

Three-dimensional models of human intestinal epithelium mimic the differentiated form and function of parental tissues often not exhibited by two-dimensional monolayers and respond to Salmonella in key ways that reflect in vivo infections. To further enhance the physiological relevance of three-dimensional models to more closely approximate in vivo intestinal microenvironments encountered by Salmonella, we developed and validated a novel three-dimensional co-culture infection model of colonic epithelial cells and macrophages using the NASA Rotating Wall Vessel bioreactor. First, U937 cells were activated upon collagen-coated scaffolds. HT-29 epithelial cells were then added and the three-dimensional model was cultured in the bioreactor until optimal differentiation was reached, as assessed by immunohistochemical profiling and bead uptake assays. The new co-culture model exhibited in vivo-like structural and phenotypic characteristics, including three-dimensional architecture, apical-basolateral polarity, well-formed tight/adherens junctions, mucin, multiple epithelial cell types, and functional macrophages. Phagocytic activity of macrophages was confirmed by uptake of inert, bacteria-sized beads. Contribution of macrophages to infection was assessed by colonization studies of Salmonella pathovars with different host adaptations and disease phenotypes (Typhimurium ST19 strain SL1344 and ST313 strain D23580; Typhi Ty2). In addition, Salmonella were cultured aerobically or microaerobically, recapitulating environments encountered prior to and during intestinal infection, respectively. All Salmonella strains exhibited decreased colonization in co-culture (HT-29-U937) relative to epithelial (HT-29) models, indicating antimicrobial function of macrophages. Interestingly, D23580 exhibited enhanced replication/survival in both models following invasion. Pathovar-specific differences in colonization and intracellular co-localization patterns were observed. These findings emphasize the power of incorporating a series of related three-dimensional models within a study to identify microenvironmental factors important for regulating infection

Dynamic Dual-Tracer MRI-Guided Fluorescence Tomography to Quantify Receptor Density In Vivo

The up-regulation of cell surface receptors has become a central focus in personalized cancer treatment; however, because of the complex nature of contrast agent pharmacokinetics in tumor tissue, methods to quantify receptor binding in vivo remain elusive. Here, we present a dual-tracer optical technique for noninvasive estimation of specific receptor binding in cancer. A multispectral MRI-coupled fluorescence molecular tomography system was used to image the uptake kinetics of two fluorescent tracers injected simultaneously, one tracer targeted to the receptor of interest and the other tracer a nontargeted reference. These dynamic tracer data were then fit to a dual-tracer compartmental model to estimate the density of receptors available for binding in the tissue. Applying this approach to mice with deep-seated gliomas that overexpress the EGF receptor produced an estimate of available receptor density of 2.3 ± 0.5 nM (n = 5), consistent with values estimated in comparative invasive imaging and ex vivo studies